This study represents the second phase of work on an ongoing project entitled Dex/CRH Response: Mood and Anxiety Disorder Endophenotype? (5 R01 MH068767). The first phase is a cross-sectional, prospective study of patterns of hormone (cortisol) response to a standard laboratory test in healthy adults. The preliminary data from the first phase characterized distinct classes of cortisol response (endophenotypes), and confirmed considerable potential for this biomarker to be valuable in detecting risk for development of mood disorders. The second phase is a prospective, longitudinal study of 200 adults to critically evaluate the role of Dex/CRH test response in prospectively predicting emotional health outcomes over 5-10 years. A cohort of 200 adults without diagnosable psychiatric disorders who have completed a baseline Dex/CRH test and an extensive battery of interview and self-report assessments in our laboratory will be followed during 5 years of funding. Subjects' historical information (history of early life adversity, family history of mental health disorders), biological data (Dex/CRH cortisol response, candidate genetic polymorphisms), psychological data (personality characteristics, resiliency features) and longitudinal assessment of ongoing and new environmental stressors will come together in a rich database which allows for examination of the intricate interactions between these variables as they relate to threshold (i.e., onset of diagnosable disorder) and subthreshold emotional health outcomes over time. The overarching goal of this research program is development of a useful biomarker that can be measured in a standard outpatient laboratory setting. We believe the Dex/CRH test could have practical value in forecasting an individual's level of risk for experiencing common and disabling mental health disorders or subsyndromal symptoms that meaningfully impact an individual's quality of life and functioning. The aims of the study are to examine the ability of the proposed endophenotype to predict outcomes independently and as part of a multidimensional model, to determine whether Dex/CRH response reflects individual sensitivity to contemporary life stressors, to evaluate the role of candidate genes in relation to the endophenotype, and to elucidate whether the symptoms/disorders which emerge in one endophenotype group are qualitatively different than those which are observed in the other group. PUBLIC HEALTH RELEVANCE: Mood and anxiety disorders are common and disabling public health problems. A valid biomarker obtainable with a standard laboratory test, that could predict risk for developing these conditions, could be widely used to assess risk in healthy adults and target interventions that might prevent the disorder onset or otherwise improve the ensuing course of mental health and wellbeing.